Abstract
PurposeCumulative evidences suggested the addition of platinum agents as neoadjuvant chemotherapy (NACT) could improve pathologic complete response (pCR) in triple-negative breast cancers (TNBC). We tried to develop a DNA homologous recombination (HR) associated gene expression score to predict tumor sensitivity to platinum-based NACT in TNBC.MethodsA retrospective cohort of 127 TNBC patients, who were diagnosed and received platinum-based NACT in Fudan University Shanghai Cancer Center from 2012 to 2017, was included in this study. By using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the expression level of eight HR associated genes was analyzed from the formalin-fixed paraffin-embedded core needle biopsy samples which obtained before NACT. A random forest model was built to estimate the weight of each gene expression level and clinical-pathological factors. The training set was used to modulate parameters and select the best model. The performance of the final model was evaluated in the validation set. ResultsA 4-gene (BRCA1, XRCC5, PARP1, RAD51) expression scoring system was developed. TNBC with higher score had nearly quadruple likelihood to achieve pCR to platinum-based NACT compared with a lower score [odds ratio (OR)=3.878; P<0.001]. At the cut-off value of -2.644, the 4-gene score system showed high sensitivity in predicting pCR in breast (93.0%) and pCR in both breast/axilla (91.8%), while, at the cut-off value of -1.969, the 4-gene score showed high specificity for pCR in breast (85.7%) and pCR in both breast/axilla (80.8%). ConclusionThe qRT-PCR-based 4-gene score has the potential to predict pCR to platinum-based NACT in TNBC.
qRT-PCR-based DNA homologous recombination-associated 4-gene score predicts pathologic complete response to platinum-based neoadjuvant chemotherapy in triple-negative breast cancer
